The nicotinic acetylcholine receptors (nAChRs) are ionotropic multi-subunit, neurotransmitter-gated receptors of the cholinergic system. These receptors are responsible for mediating the effects of the neurotransmitter acetylcholine (ACh). They are assembled from one or more α subunits (α1-α10) alone or together with one or more β subunits (β1–β4).

The receptors are also a target of the biologic compound nicotine, which mostly mimics the effects of acetylcholine on the receptors by binding as an agonist to α subunit of nAChRs.

nAChRs play critical physiologic roles in the central and peripheral nervous systems. They regulate neurotransmitter release, cell excitability, neuronal integration, and are involved in functions such as sleep and arousal patterns, fatigue, hunger, anxiety, and pain processing^1,2.

The structure of each subunit is composed of an extracellular domain, which harbors the binding site, four transmembrane α-helices (TM1–4), and a variable intracellular region⁴. The α subunits have a defining “cysteine loop” that contains two vicinal cysteine residues³.

nAChRs containing the α9 subunit are expressed in a variety of non-neuronal tissues starting from immune cells to breast carcinomas. The α9 subunit is able to form a functional homomeric receptor and in addition to co-assemble with the α10 subunit into functional heteromeric nAChRs³_.

α9-containing nAChRs play an important role in pain, inflammation, keratinocyte adhesion and in mediating synaptic transmission between the efferent olivocochlear fibers and cochlear hair cells³.

nAChRs are involved in pathologies, such as myasthenia, epilepsy, schizophrenia, Parkinson’s disease, autism, dementia with Lewy bodies, Alzheimer’s disease, and addiction³.